{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T13:58:51Z","timestamp":1766239131474,"version":"3.48.0"},"posted":{"date-parts":[[2025,12,18]]},"group-title":"Neuroscience","reference-count":58,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["DK129979"],"award-info":[{"award-number":["DK129979"]}]},{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation","doi-asserted-by":"crossref","award":["MJFF\u2013022670"],"award-info":[{"award-number":["MJFF\u2013022670"]}],"id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Parkinson\u2019s disease is increasingly understood as a disorder of distributed brain circuits, yet most imaging analyses do not explicitly respect pathway structure. We introduce a pathway-anchored, multimodal clustering framework based on Scalable Robust Variational Compositional Co-clustering (SRVCC) that integrates structural MRI, free-water\u2013corrected diffusion MRI, and DAT-SPECT in anatomically defined circuits. For each pathway, we derive a simple Multimodal Pathway Integrity Score (MPIS) that aggregates\n                  <jats:italic>z<\/jats:italic>\n                  -normalised volume, microstructural, and dopaminergic measures into an interpretable summary of imaging integrity. In the PPMI cohort, SRVCC identifies stable imaging-derived patient clusters and feature modules under explicit model selection and bootstrap\/stability checks, with covariate-adjusted analyzes controlling for age, sex, education, and medication. MPIS shows coherent but modest structure\u2013function associations: lower nigrostriatal and frontostriatal integrity relates to higher motor burden (UPDRS-III), while reduced sensory\/visuospatial and limbic integrity is linked to lower global cognition (MoCA); microvascular markers robustly stratify imaging profiles but display minimal cross-sectional coupling to these global scales. Feature-level reports highlight dominant region\u2013by\u2013modality contributors (e.g., striatal DAT-SBR, thalamic and cerebellar morphology, white-matter hyperintensity metrics), providing a transparent bridge from multimodal data to circuit-level signatures. This pathway-aware representation offers a principled, reproducible way to summarise multimodal imaging in PD and may support future work on circuit-informed stratification, prognosis, and targeted outcome measures.\n                <\/jats:p>","DOI":"10.64898\/2025.12.15.694278","type":"posted-content","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T19:20:21Z","timestamp":1766085621000},"source":"Crossref","is-referenced-by-count":0,"title":["Pathway Anchored Multimodal Clustering Reveals Circuit Level Signatures in Parkinsons Disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5671-115X","authenticated-orcid":false,"given":"Ashwin","family":"Vinod","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4549-1957","authenticated-orcid":false,"given":"Aditya Sai","family":"Ellendula","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4548-1002","authenticated-orcid":false,"given":"Shubham","family":"Bhardwaj","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1152-6436","authenticated-orcid":false,"given":"Aparna","family":"Dev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5891-4732","authenticated-orcid":false,"given":"Aaron","family":"Dominic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9619-3278","authenticated-orcid":false,"given":"Chandrajit","family":"Bajaj","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"1","key":"2025122005550748000_2025.12.15.694278v1.1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/s41531-025-00878-4","article-title":"Patient-centered brain transcriptomic and multimodal imaging determinants of clinical progression, physical activity, and treatment needs in parkinson\u2019s disease","volume":"11","year":"2025","journal-title":"npj Parkinson\u2019s Disease"},{"issue":"5","key":"2025122005550748000_2025.12.15.694278v1.2","doi-asserted-by":"crossref","first-page":"e222","DOI":"10.1016\/S2589-7500(19)30105-0","article-title":"Development and validation of the automated imaging differentiation in parkinsonism (aid-p): a multicentre machine learning study","volume":"1","year":"2019","journal-title":"The Lancet Digital Health"},{"key":"2025122005550748000_2025.12.15.694278v1.3","doi-asserted-by":"crossref","unstructured":"Brian B Avants , Leon Fonville , Olivia Hampton , Alexandra Reardon , Andrew Stenger , Xue Wang , Nicholas J Tustison , James R Stone , Philip A Cook , Barbara Marebwa , et al. 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